Cystic fibrosis (CF) is a lethal autosomal recessive disease mainly affecting white children. The risk of being a carrier of the cystic fibrosis gene in the white population is high - approximately 5%. Affected individuals with cystic fibrosis can be diagnosed by high sweat chloride levels with approximately 98% reliability. However, those individuals who carry a single cystic fibrosis gene and are potential parents of cystic fibrosis children cannot be diagnosed. For example, normal siblings of cystic fibrosis patients have a 66.6% chance of carrying one of the defective genes leading to cystic fibrosis. Such individuals and others are interested in a diagnostic test for detecting the cystic fibrosis gene. The commercial application of DNA technology toward developing a commercial test for the cystic fibrosis gene will be the long-term objective of this project. Phase I of this proposal is to identify one or more DNA polymorphisms that co-segregate with the cystic fibrosis gene because of their proximity to the gene on a human chromosome. Identification of suitable DNA polymorphisms will be made from recently constructed human genomic and chromosomal libraries. These will be utilized to study the feasibility of detecting the segregation of the CF gene in families from Texas, New York and Mexico.